Driven both by smokers? demands for safer alternatives to cigarettes and increases in cigarette sales taxes, electronic cigarettes (e-cigarettes) have witnessed a rapid growth in popularity in the last five years. While e- cigarettes may be less dangerous than traditional (or combustible) cigarettes, long-term use of this product can lead to the development and maintenance of nicotine addiction and may increase the chance of switching to traditional cigarette use. Therefore, it is important to understand the factors that may affect the addiction liability of e-cigarettes. Moreover, nicotine deposition in the lungs from the use of e-cigarettes may promote lung carcinogenesis and incomplete nicotine absorption in the body may also result in secondhand nicotine exposure. Nicotine is the primary addictive ingredient of tobacco products. Similar to other drugs of abuse, the rate and magnitude of brain nicotine accumulation are critical for the manifestation of its acute reinforcing effects. These effects are directly related to the development of conditioning, which is a driving force for nicotine self-administration in humans and the initiation and maintenance of tobacco addiction. For inhaled tobacco products, the rate of brain nicotine accumulation is dependent not only on the dose of nicotine but also on the deposition and absorption of nicotine in the respiratory tract. At present, traditional cigarettes are the most studied tobacco products in terms of addiction liability and the deposition, absorption and brain accumulation of nicotine. Despite the popularity of e-cigarettes, it has yet to be determined the extent to which nicotine delivery from e-cigarettes is comparable to that from the traditional cigarettes. The goal of the project is to directly assess the deposition, absorption and brain accumulation of 11C-nicotine from use of e-cigarettes in comparison with traditional cigarettes. Aim 1: To determine the rate of brain nicotine accumulation from e-cigarettes and to compare it with that from traditional cigarettes. Aim 2: To assess nicotine deposition in the respiratory tract from the consumption of e-cigarettes in comparison with that from smoking traditional cigarettes. Aim 3: To determine the range of nicotine absorption from use of e-cigarettes after deep inhalation (highest nicotine absorption) and after mouth holding (minimal nicotine absorption) of vapor. Exploratory Aim: To explore possible differences in brain nicotine accumulation among three types of e- liquid which vary in vapor-producing agents and pH value. This project would fill a critical gap in existing knowledge about nicotine deposition, absorption and brain accumulation from the use of e-cigarettes. Completion of this study would provide critical data for scientific evidence based policy-making for regulation of e-cigarettes to protect public health as well as for evaluation of the pros and cons of e-cigarettes as a potential smoking cessation aid.